| Background: Scutellaria baicalensis Georgi(S.baicalensis),a traditional herbal medicine,the common name Huang Qin in Chinese.S.baicalensis has multiple pharmacological effects,such as antibacterial,reduce oxidative stress damage,improve cognitive ability and alleviate of neuronal apoptosis.In our previous research,the roots of S.baicalensis extracts and its main components can prolong the lifespan and improve the metabolomics pathway disorder caused by aging of Drosophila.In addition,the roots of S.baicalensis also improve the oxidative damage,enhance memory and improve learning ability of D-gal induced aging rats.Recently,the studies of the aerial parts of S.baicalensis have attracted widespread attention.Chemical composition studies indicated that active components of the stems and leaves of S.baicalensis are mainly flavonoids.Pharmacological studies showed that it could protect hippocampal neurons,improve learning and memory,and reduce oxidative damage with age.However,the chemical constituents and pharmacological effects of flowers have been rarely reported.Therefore,this research layed a foundation for development and utilization of the flowers by studying the chemical constituents,anti-aging effects and the regulation mechanism of glutamine-glutamate metabolomics pathway.Objective: 1.Analyze the chemical constituents of the S.baicalensis flowers and evaluate its anti-oxidation ability in vitro;2.The anti-aging effect of the S.baicalensis flowers were investigated in D-gal induced aging rats;3.The potential anti-aging mechanism of the S.baicalensis flowers based on NMR metabolomics;4.Quantitative the main metabolic pathways of the S.baicalensis flowers anti-aging.Methods: 1.The chemical constituents of the S.baicalensis flowers were analyzed by LC-MS;the antioxidant activity in vitro were determined by hydroxyl radical(·OH)and superoxide anion radicals(O2-·)clearance rate according to the kit instructions.2.Rats were randomly divided into six groups: Control group,D-gal group as well as S.baicalensis flowers and S.baicalensis roots groups.Except for the Control group,the rats were intraperitoneal daily injected with D-gal(300 mg kg-1 day-1)for 7 weeks,while rats in the control group received the equal dose of 0.9% physiological saline.The intervention groups were treated with S.baicalensis flowers dissolved in water at two doses of 0.4 and 0.8 g/kg respectively by oral administration after injection of D-gal during the entire experiments.The positive control groups were treated with S.baicalensis roots at two doses of 0.4 and 0.8 g/kg respectively.In order to explore the anti-aging efficacy of the S.baicalensis flowers,the rat behaviors were observed by morris water maze and open field experiments.And the biochemical indicators related to aging in serum such as superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-px)and advanced glycation end products(AGEs)were determined by commercial kits.On this basis,the protective effects of flowers on the liver of aging rats were further studied by observing the organ index,HE staining and oxidative damage.3.The metabolic profile changes of serum and liver in aging rats after flowers intervention were analyzed by nuclear magnetic metabolomics technique.The differential metabolites were found by multivariate statistical analysis and imported into the metaboanalyst database for pathway analysis.4.The most correlated metabolic pathway with aging was verified by enzyme-linked immunosorbent assay.Result: 1.The chemical composition of flowers were analyzed by UPLCMS,and 19 components were clearly detected.The high contents were apigenin,chrysin,scutellarin,isocarthamidin-7-O-glu acid and baicalin.In addition,the results of antioxidant experiments showed that the clearance rates of 4 mg·m L-1 of flowers to ·OH and O2-· were 85% and 57%,respectively,indicating that flowers has antioxidant capacity.2.S.baicalensis flowers could significantly improve the cognitive ability and autonomic activity of aging rats,modulate the SOD(p<0.001,p<0.001),GSH-px(p<0.001,p<0.001)activities and MDA(p<0.05),AGEs(p<0.001,p<0.001)contents,improve oxidative damage.The anti-aging efficacy of flowers was slightly better than roots at the same dose.Moreover,S.baicalensis flowers could protect the liver of aging rats by improving oxidative damage of rat liver.3.The serum and liver metabolomics of aging rats showed that glutamineglutamate metabolism was most correlated with aging and significantly was modulated after the S.baicalensis flowers administration.4.The key metabolites of glutamine-glutamate metabolism were verified.The levels of Gln and Glu(p<0.001)in serum of D-gal group rats were significantly increased compared with the control group;the levels of Gln and Glu(p<0.001)in liver of D-gal group rats were significantly decreased compared with the control group,and administration of the S.baicalensis flowers could significantly reverse respectively.Meanwhile,the glutamineglutamate metabolism disorder may result in the change of the synthesis ability of glutathione(GSH)in liver.This study showed that the synthesis ability of GSH in liver of aging rats were decreased,and the synthesis ability was significantly enhanced after the intervention of S.baicalensis flowers(p<0.001,p<0.001).Conclusion: 1.The S.baicalensis flowers has a large number of flavonoids and antioxidant capacity.2.The S.baicalensis flowers could improve the cognitive impairment,autonomic activity and oxidative damage of aging rats,and the anti-aging efficacy of flowers is slightly better than roots at the same dose.In addition,it also improve liver organ index,oxidative damage and cell morphology of the liver.3.The glutamine-glutamate metabolism maybe an important factor in process of aging,and S.baicalensis flowers could regulate this metabolic pathway.4.The quantitative results of Gln and Glu in serum and liver of rats were consistent with the results of metabolomics research.The contents of Gln and Glu in the serum of D-gal group were significantly increased and significantly decreased in liver.Compared with the control group,the synthesis ability of GSH in liver was decreased.Nevertheless,the S.baicalensis flowers could significantly reverse the contents of Gln and Glu in serum and liver of rats,increase GSH activity in liver. |
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